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Endişe verici bir madde: Bir prodrug olan 1,4-Bütandiol suistimali

Yıl 2021, Cilt: 35 Sayı: 2, 86 - 91, 31.08.2021
https://izlik.org/JA28CA57ZN

Öz

Prodrug kavramı vücuda alımından sonra metabolize olarak farmakolojik olarak aktif hale geçen bileşiklere verilen isimdir. 1,4-bütandiol kimya, plastik ve tekstil sanayii gibi alanlarda yaygın kullanımı olan bir maddedir. Vücuda alındıktan sonra hızla psikoaktif etki gösteren Gama-Hidroksibütirat ’a dönüştüğünden dolayı “prodrug” lar için tipik örnektir. Son zamanlarda bu maddenin suiistimal edildiği adli dosyalar içerisinden görülmektedir. Maddenin psikoaktif etkileri ağızdan alımını takiben 5 ile 20 dakika içerisinde başlayıp yaklaşık olarak 2 ile 3 saat kadar sürmektedir. Oluşturduğu etkiler arasında öfori, erotik uyarılmalar, inhibisyon kaybı ve daha fazla tüketildiğinde sedatif etki sayılabilir. Bu makalede kendisi bizatihi psikoaktif bir etki doğurmayan 1,4-bütandiol’ün artan suiistimal potansiyelini ve yapılması gerekenleri ele almak amaçlanmıştır. 1,4-bütandiol Avrupa Birliği Kozmetik Maddeler mevzuatında, tehlikeli maddeler sınıfında yer almadığı gibi 1988 Uyuşturucu ve Psikotrop Maddelerin Kaçakçılığına Karşı Birleşmiş Milletler Sözleşmesi’nde, Birleşmiş Milletler prekürsör kimyasallar listesinde de bulunmamaktadır. Oysa bu maddenin metaboliti Gama-Hidroksibütirat 1971 psikotrop maddeler sözleşmesinin 2 nolu listesinde yer almaktadır. Günümüzde uyuşturucu tacirlerinin hukuki müeyyidelerden kaçmak amacı ile yeni yöntemler sergiledikleri görülmektedir. Bu nedenle Türk Ceza Kanunu’nun 188. maddesine ilave bir fıkra eklemek sureti ile ya da mevcut fıkralarda düzenleme yapılarak “prodrug” ların yasa kapsamına alınmasının önü açılmalıdır.

Kaynakça

  • Rautio J, Meanwell NA, Di L, Hageman MJ. The expanding role of prodrugs in contemporary drug design and development. Na- ture Reviews. Drug Discovery 2018;17 8 :559-87.
  • Rautio J, Kumpulainen H, Heimbach T, Oliyai R, , Järvinen D Savolainen T. Prodrugs: design and clinical applications. J.Nat Rev Drug Discov 2008;7 3 :255-70.
  • Sprince H, Josephs Jr JA, Wilpizeski CR. Neuropharmacologi- cal effects of 1,4-butanediol and related congeners compared with those of Gama Hidroksibütirat and gamma-butyrolactone. Life Sciences 1966;5:2041-52.
  • The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals., 13 th. Edition. MerckCo.,Inc., NJ. 2001.
  • World Health Organization. 1,4-Butanediol 1,4-BD Pre-Re- view Report: Expert Committee on Drug Dependence Thirty-fifth Meeting. Geneva: World Health Organization; 2012. Report No.: th ECDD 2012 Agenda item 5.5.
  • World Health Organization. 1,4-Butanediol 1,4-BD Critical Review Report: Expert Committee on Drug Dependence Thirty- sixth Meeting. Geneva:16-20 June, World Health Organization; Report No.: 36th ECDD 2014 Agenda item 4.4 .
  • https://psychonautwiki.org/wiki/1,4-Butanediol Cited: 15 Au- gust 2021 .
  • Thai D, Dyer JE, Jacop P, Haller CA. Clinical pharmacology of ,4 butanediol and gamma –hydroxybutyrate after oral 1,4 bu- tanediol administration to healty volunteers. Clin Pharmacol Ther 2007;81 2 :178-84.
  • Poldrugo F, Snead OC. 1,4 butanediol, Ɣ-hydroxybutyric acid and ethanol: Relationships and interections. Neuropharmacol- ogy 1984;59 23 :109-13.
  • https://www.who.int/medicines/areas/quality_safety/4_4_ Review.pdf Cited: 15 August 2021
  • Schep LJ, Knudsen K, Slaughter RJ, Vale JA, Mégarbane B. The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and ,4-butanediol. Clin Toxicol Phila 2012;50 6 :458-70.
  • Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001;344:87-94.
  • Palmer RB. Gamma-butyrolactone and 1,4-butanediol: Abused analogues of gamma-hydroxybutyrate. Toxicol Rev ;23:21-31.
  • https://en.wikipedia.org/wiki/Bindeez Cited: 15 August 2021
  • Linda Wang. Industrial Chemical sullies popular children’s toy. 1,4 butanediol rapidly converts to gamma –hydroxybutyric acid in the body. Chemical and Engeneering News, November 9th., 2007 https://cen.acs.org/articles/85/web/2007/11/Industrial-Chemical-Sullies-Popular-Childrens.html Cited: 15 August 2021
  • Suchard J, Nizkorodov S, Wilkinson S. 1,4-Butanediol content of aqua dots children’s craft toy beads. J Med Toxicol 2009;5:120- 4.
  • Gunja N, Doyle E, Carpenter K, Chan OT, Gilmore S, Browne G, Graundis A. Gama Hidroksibütirat poisoning from toy beads. Med J Aust 2008;188:54-5.
  • Carai MA, Quang LS, Atzeri S, Lobina C, Maccioni P, Orru A, Gessa GL, Maher TJ, Colombo G. Withdrawal syndrome from gamma-hydroxybutyric acid GHB and 1,4-butanediol 1,4-BD in Sardinian alcohol-preferring rats. Brain Res Brain Res Protoc 2005;15:75-8.
  • Goodwin AK, Gibson KM, Weerts EM. Physical dependence on gamma-hydroxybutrate GHB prodrug 1,4-butanediol 1,4- BD : Time course and severity of withdrawal in baboons. Drug and Alcohol Dependence 2013;132:427-33.
  • Mycyk MB, Wilemon C, Aks SE. Two cases of withdrawal from 1,4-butanediol use. Annals of Emergency Medicine 2001;38:345- 6.
  • Wojtowicz JM, Yarema MC, Wax PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. Canadian Journal of Emergency Medicine 2008;10:69-74.
  • EMCDDA Action on new drugs 2011. Early warning system on new synthetic drugs: Summary on GHB based on the EWS Final Reports 2011. Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction EMCDDA , 2011.
  • European Monitoring Centre for Drugs and Drug Addiction. Report on the Risk Assessment of GHB in the Framework of the Joint Action on New Synthetic Drugs. Luxembourg: European Monitoring Centre for Drugs and Drug Addiction, 2002.
  • Schwarz W, Schossig J, Rossbacher R, Pinkos R, Höke H. Butyrolactone. Ullmann’s Encyclopedia of Industrial Chemistry. Wheinheim: Wiley-VCH, 2019.

An alarming substance: Abuse of a prodrug, 1,4-Butanediol

Yıl 2021, Cilt: 35 Sayı: 2, 86 - 91, 31.08.2021
https://izlik.org/JA28CA57ZN

Öz

A prodrug is a compound that, after administration, is metabolized and converted within the body into a pharmacologically active drug. 1,4-butanediol is widely used in industry such as chemical, plastics and textile. It is typical example of prodrugs, because of rapidly metabolized to psychoactive gamma-hydroxybutyrate after consumed. It is recently seen from our forensic case files that it is abused. After administered orally, its psychoactive effects start in 5 to 20 minutes, and last for approximately 2 to 3 hours. The actual effects are euphoric, erotic senses, loss of inhibitions and after a dose of 4 ml, it induces sedative effect. In this article, it is aimed to discuss the increasing abuse potential of 1,4-butanediol, which itself does not cause a psychoactive effect, and what needs to be done. 1,4- butanediol is not restricted under the European legislation on cosmetics, not classified as a dangerous substance, and it is not included in the tables of the 1988 UN Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The chemical is not subject to the key UN convention that covers precursor chemicals; however, its metabolite, γ-hydroxybutyrate, is currently in Schedule II of the 1971 Convention. Today, it is seen that drug dealers exhibit new methods in order to escape from legal sanctions. For this reason, by adding an additional paragraph to Article 188 of the Turkish Penal Code or by making arrangements in the existing paragraphs, it should be possible to include “prodrugs” within the scope of the law.

Kaynakça

  • Rautio J, Meanwell NA, Di L, Hageman MJ. The expanding role of prodrugs in contemporary drug design and development. Na- ture Reviews. Drug Discovery 2018;17 8 :559-87.
  • Rautio J, Kumpulainen H, Heimbach T, Oliyai R, , Järvinen D Savolainen T. Prodrugs: design and clinical applications. J.Nat Rev Drug Discov 2008;7 3 :255-70.
  • Sprince H, Josephs Jr JA, Wilpizeski CR. Neuropharmacologi- cal effects of 1,4-butanediol and related congeners compared with those of Gama Hidroksibütirat and gamma-butyrolactone. Life Sciences 1966;5:2041-52.
  • The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals., 13 th. Edition. MerckCo.,Inc., NJ. 2001.
  • World Health Organization. 1,4-Butanediol 1,4-BD Pre-Re- view Report: Expert Committee on Drug Dependence Thirty-fifth Meeting. Geneva: World Health Organization; 2012. Report No.: th ECDD 2012 Agenda item 5.5.
  • World Health Organization. 1,4-Butanediol 1,4-BD Critical Review Report: Expert Committee on Drug Dependence Thirty- sixth Meeting. Geneva:16-20 June, World Health Organization; Report No.: 36th ECDD 2014 Agenda item 4.4 .
  • https://psychonautwiki.org/wiki/1,4-Butanediol Cited: 15 Au- gust 2021 .
  • Thai D, Dyer JE, Jacop P, Haller CA. Clinical pharmacology of ,4 butanediol and gamma –hydroxybutyrate after oral 1,4 bu- tanediol administration to healty volunteers. Clin Pharmacol Ther 2007;81 2 :178-84.
  • Poldrugo F, Snead OC. 1,4 butanediol, Ɣ-hydroxybutyric acid and ethanol: Relationships and interections. Neuropharmacol- ogy 1984;59 23 :109-13.
  • https://www.who.int/medicines/areas/quality_safety/4_4_ Review.pdf Cited: 15 August 2021
  • Schep LJ, Knudsen K, Slaughter RJ, Vale JA, Mégarbane B. The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and ,4-butanediol. Clin Toxicol Phila 2012;50 6 :458-70.
  • Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001;344:87-94.
  • Palmer RB. Gamma-butyrolactone and 1,4-butanediol: Abused analogues of gamma-hydroxybutyrate. Toxicol Rev ;23:21-31.
  • https://en.wikipedia.org/wiki/Bindeez Cited: 15 August 2021
  • Linda Wang. Industrial Chemical sullies popular children’s toy. 1,4 butanediol rapidly converts to gamma –hydroxybutyric acid in the body. Chemical and Engeneering News, November 9th., 2007 https://cen.acs.org/articles/85/web/2007/11/Industrial-Chemical-Sullies-Popular-Childrens.html Cited: 15 August 2021
  • Suchard J, Nizkorodov S, Wilkinson S. 1,4-Butanediol content of aqua dots children’s craft toy beads. J Med Toxicol 2009;5:120- 4.
  • Gunja N, Doyle E, Carpenter K, Chan OT, Gilmore S, Browne G, Graundis A. Gama Hidroksibütirat poisoning from toy beads. Med J Aust 2008;188:54-5.
  • Carai MA, Quang LS, Atzeri S, Lobina C, Maccioni P, Orru A, Gessa GL, Maher TJ, Colombo G. Withdrawal syndrome from gamma-hydroxybutyric acid GHB and 1,4-butanediol 1,4-BD in Sardinian alcohol-preferring rats. Brain Res Brain Res Protoc 2005;15:75-8.
  • Goodwin AK, Gibson KM, Weerts EM. Physical dependence on gamma-hydroxybutrate GHB prodrug 1,4-butanediol 1,4- BD : Time course and severity of withdrawal in baboons. Drug and Alcohol Dependence 2013;132:427-33.
  • Mycyk MB, Wilemon C, Aks SE. Two cases of withdrawal from 1,4-butanediol use. Annals of Emergency Medicine 2001;38:345- 6.
  • Wojtowicz JM, Yarema MC, Wax PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. Canadian Journal of Emergency Medicine 2008;10:69-74.
  • EMCDDA Action on new drugs 2011. Early warning system on new synthetic drugs: Summary on GHB based on the EWS Final Reports 2011. Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction EMCDDA , 2011.
  • European Monitoring Centre for Drugs and Drug Addiction. Report on the Risk Assessment of GHB in the Framework of the Joint Action on New Synthetic Drugs. Luxembourg: European Monitoring Centre for Drugs and Drug Addiction, 2002.
  • Schwarz W, Schossig J, Rossbacher R, Pinkos R, Höke H. Butyrolactone. Ullmann’s Encyclopedia of Industrial Chemistry. Wheinheim: Wiley-VCH, 2019.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Adli Biyoloji
Bölüm Araştırma Makalesi
Yazarlar

Faruk Aşıcıoğlu Bu kişi benim

Gönderilme Tarihi 1 Ocak 2021
Yayımlanma Tarihi 31 Ağustos 2021
IZ https://izlik.org/JA28CA57ZN
Yayımlandığı Sayı Yıl 2021 Cilt: 35 Sayı: 2

Kaynak Göster

Vancouver 1.Faruk Aşıcıoğlu. Endişe verici bir madde: Bir prodrug olan 1,4-Bütandiol suistimali. ATD [Internet]. 01 Ağustos 2021;35(2):86-91. Erişim adresi: https://izlik.org/JA28CA57ZN

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